INT65245

Context Info Confidence 0.78 First Reported 1996 Last Reported 2010 Negated 4 Speculated 8 Reported most in Body Documents 121 Total Number 143 Disease Relevance 98.14 Pain Relevance 41.56

mitochondrion (Nos3) Golgi apparatus (Nos3) cytoplasm (Nos3) signal transduction (Nos3) oxidoreductase activity (Nos3) nucleolus (Nos3)

Anatomy Link Frequency spinal cord 11 sciatic nerve 8 neuronal 6 endothelial cells 6 blood 3 Nos3 (Mus musculus)

Pain Link Frequency Relevance Heat Spinal cord 1243 99.98 acular 300 99.92 dorsal root ganglion 363 99.80 Neuronal nitric oxide synthase 22 99.76 aspirin 174 99.56 Neuropathic pain 582 99.52 Pain 795 99.44 Sciatic nerve 1487 99.40 Tetrahydrobiopterin 166 99.32 ischemia 82 99.32

Disease Link Frequency Relevance Heat Targeted Disruption 2641 99.96 Disorder Of Lipid Metabolism 751 99.82 Ganglion Cysts 379 99.80 Nervous System Injury 1194 99.74 Hypertension 803 99.60 Injury 564 99.60 Neuropathic Pain 1311 99.52 Uremia 8 99.52 Cancer 218 99.48 Stress 500 99.46

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Using epithelial HeLa cells expressing the endothelial NO synthase we show that ibuprofen-arginine releases NO and that this NO protects against the cytotoxic apoptogenic effects of staurosporine.

Gene_expression (expressing) of endothelial NO synthase in HeLa

1) Confidence 0.78 Published 2009 Journal Pharmacol. Res. Section Abstract Doc Link 19539763 Disease Relevance 0.73 Pain Relevance 0.41

It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and endothelial function involves increased expression of endothelial nitric oxide synthase (eNOS).

Gene_expression (expression) of endothelial nitric oxide synthase

2) Confidence 0.78 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.55 Pain Relevance 0.14

It has also been demonstrated that the molecular mechanism by which Waon therapy improves vascular flow and endothelial function involves increased expression of endothelial nitric oxide synthase (eNOS).

Gene_expression (expression) of eNOS

3) Confidence 0.78 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.55 Pain Relevance 0.14

Our results revealed that the mRNA expression of inducible nitric oxide synthase (iNOS) was reduced by approximately 50% in GEB-pretreated mice versus the controls, whereas the mRNA expression levels of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) remained unchanged.

Gene_expression (expression) of eNOS in neuronal associated with neuronal nitric oxide synthase

4) Confidence 0.76 Published 2007 Journal Int. J. Mol. Med. Section Abstract Doc Link 17611639 Disease Relevance 0.46 Pain Relevance 0.14

Another interesting finding in the present study is the correlation between nNOS and eNOS expression in the placebo, but not in the ketorolac treatment group, which suggests an inhibitory effect of ketorolac on eNOS gene expression.

Gene_expression (expression) of eNOS gene associated with acular

5) Confidence 0.73 Published 2010 Journal Mol Pain Section Body Doc Link PMC2949722 Disease Relevance 0.45 Pain Relevance 0.63

The down regulation of eNOS by NSAIDs, on the other hand, is in line with the suppression of eNOS expression by high-dose aspirin or meloxicam, in retinas of diabetic rats [36].

Gene_expression (expression) of eNOS in retinas associated with aspirin, diabetes mellitus and cinod

6) Confidence 0.73 Published 2010 Journal Mol Pain Section Body Doc Link PMC2949722 Disease Relevance 0.54 Pain Relevance 0.91

Another interesting finding in the present study is the correlation between nNOS and eNOS expression in the placebo, but not in the ketorolac treatment group, which suggests an inhibitory effect of ketorolac on eNOS gene expression.

Gene_expression (expression) of eNOS associated with acular

7) Confidence 0.73 Published 2010 Journal Mol Pain Section Body Doc Link PMC2949722 Disease Relevance 0.47 Pain Relevance 0.57

Meanwhile, Western blot showed that eNOS expression in the spinal cord of nNOS knockout mice was up-regulated compared with wild-type mice; immunohistochemical staining showed that the spinal eNOS was mainly distributed in superficial laminae of the dorsal horn.

Gene_expression (expression) of eNOS in dorsal horn associated with targeted disruption, dorsal horn and spinal cord

8) Confidence 0.73 Published 2004 Journal Neuroscience Section Abstract Doc Link 15350652 Disease Relevance 0.99 Pain Relevance 0.64

Consistent with this observation, lung homogenates from female mice contained greater eNOS protein expression when compared to lung homogenates from male mice (Figure 3A).

Gene_expression (expression) of eNOS in lung

9) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2982841 Disease Relevance 0 Pain Relevance 0

Furthermore, in a mouse model of hindlimb ischemia, repeated Waon therapy increased eNOS protein expression, blood flow, and capillary density.

Gene_expression (expression) of eNOS in blood associated with ischemia

10) Confidence 0.68 Published 2010 Journal Circ. J. Section Abstract Doc Link 20154403 Disease Relevance 0.63 Pain Relevance 0.15

However, while the disruption of NOS1 gene did not alter the mRNA or protein levels of NOS2 in sham-operated mice a significant increase in the spinal cord expression of NOS3 was further demonstrated in sham-operated NOS1-KO mice [18].

Gene_expression (expression) of NOS3 in spinal cord associated with targeted disruption and spinal cord

11) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.13 Pain Relevance 0.85

Expression of NOS3 in the spinal cord of WT, NOS2-KO and NOS1-KO mice

Gene_expression (Expression) of NOS3 in spinal cord associated with targeted disruption and spinal cord

12) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 0.94 Pain Relevance 0.55

These results indicated that the compensatory changes in the spinal cord expression of NOS3 in NOS1-KO under basal conditions does not fully compensate for NOS1 function in neuropathic pain, which is mainly produced by NOS2.

Gene_expression (expression) of NOS3 in spinal cord associated with targeted disruption, neuropathic pain and spinal cord

13) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.04 Pain Relevance 0.84

Our results did not show significant changes in the expression of NOS2 and NOS3, mRNA and protein, on day 21th after sciatic nerve injury.

Gene_expression (expression) of NOS3 in sciatic nerve associated with nervous system injury and sciatic nerve

14) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 0.86 Pain Relevance 0.77

Sciatic nerve injury also increases the spinal cord expression of NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively.

Gene_expression (expression) of NOS3 in NOS1 associated with targeted disruption, nervous system injury, sciatic nerve and spinal cord

15) Confidence 0.67 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3001461 Disease Relevance 1.77 Pain Relevance 1.06

The possible alterations in NOS2 and NOS3 expression induced by neuropathic pain have been also evaluated in this study.

Gene_expression (expression) of NOS3 associated with neuropathic pain

16) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 0.86 Pain Relevance 0.75

The mRNA and protein levels of NOS1, NOS2 and NOS3 in the spinal cord of WT and KO mice, at 21 days after surgery, were also assessed.

Gene_expression (levels) of NOS3 in spinal cord associated with targeted disruption and spinal cord

17) Confidence 0.67 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3001461 Disease Relevance 1.80 Pain Relevance 1.00

Our data also indicate that the enhanced spinal cord expression of NOS3 in NOS1-KO mice might compensates for the lack of NOS1 under basal conditions but not after sciatic nerve ligation.

Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption, sciatic nerve and spinal cord

18) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.48 Pain Relevance 0.91

Several works have demonstrated that nerve injury after sciatic nerve ligation evoked an increased NOS1 and NOS2, but not of NOS3, protein expression in the ipsilateral site of the dorsal root ganglia and the sciatic nerve [4], [6]–[11].

Gene_expression (expression) of NOS3 in sciatic nerve associated with nervous system injury and sciatic nerve

19) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.48 Pain Relevance 1.16

In the present study, we also demonstrated that no compensatory changes in the spinal cord expression of NOS3 take place in sciatic nerve-injured NOS1 and NOS2 knockout mice as well as in sham-operated NOS2-KO mice [12].

Gene_expression (expression) of NOS3 in sciatic nerve associated with targeted disruption, sciatic nerve and spinal cord

20) Confidence 0.67 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001461 Disease Relevance 1.35 Pain Relevance 0.88

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